Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.
Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.
Mol Nutr Food Res. 2023 Jun;67(11):e2200755. doi: 10.1002/mnfr.202200755. Epub 2023 Apr 25.
The purpose of this research is to investigate the specific role of HSP90 paralogs in ulcerative colitis (UC), and to explore the mechanisms behind the inhibitory effects of galangin (Gal) on UC by inhibiting HSP90β in vivo.
In order to achieve this, publicly available gene expression data and molecular biology techniques are used. The results show that the expression of HSP90β is significantly increased in the mucosal biopsies of UC patients and in the colons of colitis mice, and that there is a significant correlation between HSP90β levels and disease severity. Then, Gal is found to bind directly to HSP90β and downregulates the level of p-AKT, as well as the stability and oligomerization of HSP90β, indicating Gal as an HSP90β inhibitor. Moreover, the findings reveal that HSP90β plays a critical role in controlling UC, and that Gal can alleviate colitis by inhibiting HSP90β and perturbing fatty acid synthesis-mediated NLRP3 inflammasome activation.
These results not only provide insight into the potential therapeutic use of Gal in the treatment of UC, but also offer new perspectives on the role of HSP90β in this disease.
本研究旨在探讨热休克蛋白 90（HSP90）同工型在溃疡性结肠炎（UC）中的具体作用，并通过体内抑制 HSP90β来探索白杨素（Gal）抑制 UC 的机制。
为了实现这一目标，使用了公开的基因表达数据和分子生物学技术。结果表明，UC 患者的黏膜活检组织和结肠炎小鼠的结肠中 HSP90β 的表达显著增加，并且 HSP90β 水平与疾病严重程度之间存在显著相关性。然后，发现 Gal 可直接与 HSP90β 结合，并下调 p-AKT 水平以及 HSP90β 的稳定性和寡聚化，表明 Gal 是 HSP90β 的抑制剂。此外，研究结果表明 HSP90β 在控制 UC 中发挥关键作用，Gal 可通过抑制 HSP90β 和扰乱脂肪酸合成介导的 NLRP3 炎性体激活来缓解结肠炎。
这些结果不仅为 Gal 在治疗 UC 中的潜在治疗用途提供了新的见解，也为 HSP90β 在这种疾病中的作用提供了新的视角。
